Nuevas estrategias terapéuticas en diabetes mellitus tipo 1

El principal determinante del riesgo de complicaciones derivadas de la diabetes mellitus tipo 1 se debe a los altos niveles de glucosa en sangre mantenidos durante largo tiempo. Para conseguir un beneficio terapéutico en pacientes con diabetes mellitus es necesario desarrollar tratamientos que permitan de manera segura, efectiva y estable mantener la normoglucemia. Lamentablemente, el tratamiento de la diabetes mellitus tipo 1 mediante el aporte exógeno de insulina no es capaz de conseguir niveles estables de glucosa en sangre, de manera que con frecuencia se producen casos de severa hipoglucemia o hiperglucemia. Hasta la fecha la única solución para reestablecer de manera permanente la normoglucemia se consigue mediante el trasplante de páncreas o de islotes pancreáticos. Sin embargo, a medida que se incrementa el número de centros especializados en el trasplante de islotes, mayor es la necesidad de islotes para su trasplante. Así pues, el estudio de nuevas fuentes de células productoras de insulina así como de nuevos tratamientos que permitan preservar o incluso aumentar la masa de células beta en los pacientes con diabetes mellitus representa un objetivo de primera necesidad en este campo. En este sentido, en la última década ha habido un avance significativo en el campo de la biología de las células madre. Sin embargo, la identificación de células apropiadas para la generación de nuevas células beta, además del desarrollo de técnicas para la caracterización de estas células, así como de ensayos y modelos animales apropiados para probar su capacidad de diferenciación tanto in vitro como in vivo son de vital importancia para la puesta en marcha de nuevas estrategias terapéuticas basadas en la aplicación de las células madre para el tratamiento de la diabetes mellitus tipo 1

Experimental investigation of the effect of orifices inclination angle in multihole diesel injector nozzles. Part-1-Hydraulic performance

[EN] Nozzle hydraulic performance has a significant impact on diesel spray development and combustion characteristics. Thus, it is important to understand the links between the nozzle geometry, the internal flow features and the spray formation. In this paper, a detailed analysis of the impact of the nozzle orifices inclination angle on its hydraulic performance is performed. For this purpose, three different nozzles with included angles of 90, 140 and 155 degrees are evaluated. Instantaneous injection rate and momentum flux are measured on a set of injector operating conditions (mainly injection pressure and discharge pressure). The results show that higher inclination angles lead to smaller mass flow and momentum flux at steady-state conditions, due to the higher losses at the orifice inlet. These losses are translated in lower both area and velocity coefficients. Nevertheless, the impact of this parameter is limited thanks to the counter-acting effect of the hydrogrinding process, which produces larger rounding radii at the orifice inlet as the included angle increases. Based on the experimental results, correlations of the discharge coefficient as a function of the Reynolds number are obtained and evaluated. (C) 2017 Elsevier Ltd. All rights reserved.This work was partly sponsored by "Ministerio de Economia y Competitividad", of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor", Reference TRA2015-67679-c2-1-R.Salvador, FJ.; López, JJ.; De La Morena, J.; Crialesi Esposito, M. (2018). Experimental investigation of the effect of orifices inclination angle in multihole diesel injector nozzles. Part-1-Hydraulic performance. Fuel. 213:207-214. https://doi.org/10.1016/j.fuel.2017.04.019S20721421

Leptin Inhibits Angiotensin II-Induced Intracellular Calcium Increase and Vasoconstriction in the Rat Aorta

Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation

Mycorrhizal symbiosis primes the accumulation of antiherbivore compounds and enhances herbivore mortality in tomato

Plant association with arbuscular mycorrhizal fungi (AMF) can increase their ability to overcome multiple stresses, but their impact on plant interactions with herbivorous insects is controversial. Here we show higher mortality of the leaf-chewer Spodoptera exigua when fed on tomato plants colonized by the AMF Funneliformis mosseae, evidencing mycorrhiza-induced resistance. In search of the underlying mechanisms, an untargeted metabolomic analysis through ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was performed. The results showed that mycorrhizal symbiosis had a very limited impact on the leaf metabolome in the absence of stress, but significantly modulated the response to herbivory in the damaged area. A cluster of over accumulated metabolites was identified in those leaflets damaged by S. exigua feeding in mycorrhizal plants, while unwounded distal leaflets responded similar to those from non-mycorrhizal plants. These primed-compounds were mostly related to alkaloids, fatty acid derivatives and phenylpropanoid-polyamine conjugates. The deleterious effect on larval survival of some of these compounds, including the alkaloid physostigmine, the fatty acid derivatives 4-oxododecanedioic acid and azelaic acid, was confirmed. Thus, our results evidence the impact of AMF on metabolic reprograming upon herbivory that leads to a primed accumulation of defensive compounds

Study of turbulence in atomizing liquid jets

[EN] Among the many unknowns in the study of atomizing sprays, defining an unambiguous way to analyze turbulence is, perhaps, one of the most limiting ones. The lack of proper tools for the analysis of the turbulence field (e.g. specific one/two-point statistics, spectrum, structure functions) limits the understanding of the overall phenomenon occurring, impeding the correct estimation of motion scales (from the Kolmogorov one to the integral one). The present work proposes a methodology to analyze the turbulence in atomizing jets using a pseudo-fluid method. The many challenges presented in these types of flows (such as temporal fluid properties uncertainties, strong anisotropy and lack of a priori chance of determining the motion scales) can be simplified by such a method, as it will be clearly shown by the smooth results obtained. Finally, the method is tested against the one-phase flows turbulent data available in the literature for the Kolmogorov scaling of the one-dimension energy spectra, showing how a pseudo-fluid method could provide a reliable tool to analyze multiphase turbulence, especially in spray's primary atomization.This research has been partially funded by Spanish Ministerio de Economia y Competitividad through project RTI2018-099706-B-100, "Estudio de la atomizacion primaria mediante simulaciones DNS y tecnicas opticas de muy alta resolucion". Additionally, the authors thankfully acknowledge the computer resources at MareNostrum 4 (Barcelona Supercomputing Center) and their technical support provided by FI-2017-2-0035 and TITAN (Oak Ridge Leadership Computing Facility) in the frame of the project TUR124.Torregrosa, AJ.; Payri, R.; Salvador, FJ.; Crialesi-Esposito, M. (2020). Study of turbulence in atomizing liquid jets. International Journal of Multiphase Flow. 129:1-12. https://doi.org/10.1016/j.ijmultiphaseflow.2020.103328S112129Agbaglah, G., Chiodi, R., & Desjardins, O. (2017). Numerical simulation of the initial destabilization of an air-blasted liquid layer. Journal of Fluid Mechanics, 812, 1024-1038. doi:10.1017/jfm.2016.835Aliseda, A., Hopfinger, E. J., Lasheras, J. C., Kremer, D. M., Berchielli, A., & Connolly, E. K. (2008). Atomization of viscous and non-newtonian liquids by a coaxial, high-speed gas jet. Experiments and droplet size modeling. International Journal of Multiphase Flow, 34(2), 161-175. doi:10.1016/j.ijmultiphaseflow.2007.09.003Antonia, R. A., Anselmet, F., & Chambers, A. J. (1986). Assessment of local isotropy using measurements in a turbulent plane jet. Journal of Fluid Mechanics, 163, 365-391. doi:10.1017/s0022112086002331Bassenne, M., Esmaily, M., Livescu, D., Moin, P., & Urzay, J. (2019). 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Study of mass and momentum transfer in diesel sprays based on X-ray mass distribution measurements and on a theoretical derivation. Experiments in Fluids, 50(2), 233-246. doi:10.1007/s00348-010-0919-8Pitsch, H., & Desjardins, O. (2010). DETAILED NUMERICAL INVESTIGATION OF TURBULENT ATOMIZATION OF LIQUID JETS. Atomization and Sprays, 20(4), 311-336. doi:10.1615/atomizspr.v20.i4.40Dodd, M. S., & Ferrante, A. (2016). On the interaction of Taylor length scale size droplets and isotropic turbulence. Journal of Fluid Mechanics, 806, 356-412. doi:10.1017/jfm.2016.550Duret, B., Luret, G., Reveillon, J., Menard, T., Berlemont, A., & Demoulin, F. X. (2012). DNS analysis of turbulent mixing in two-phase flows. International Journal of Multiphase Flow, 40, 93-105. doi:10.1016/j.ijmultiphaseflow.2011.11.014Elghobashi, S. (2019). Direct Numerical Simulation of Turbulent Flows Laden with Droplets or Bubbles. Annual Review of Fluid Mechanics, 51(1), 217-244. doi:10.1146/annurev-fluid-010518-040401Gauding, M., Danaila, L., & Varea, E. (2018). One-point and two-point statistics of homogeneous isotropic decaying turbulence with variable viscosity. International Journal of Heat and Fluid Flow, 72, 143-150. doi:10.1016/j.ijheatfluidflow.2018.05.013Gorokhovski, M., & Herrmann, M. (2008). Modeling Primary Atomization. Annual Review of Fluid Mechanics, 40(1), 343-366. doi:10.1146/annurev.fluid.40.111406.102200Gréa, B.-J., Griffond, J., & Burlot, A. (2014). The effects of variable viscosity on the decay of homogeneous isotropic turbulence. Physics of Fluids, 26(3), 035104. doi:10.1063/1.4867893Harris, V. G., Graham, J. A. H., & Corrsin, S. (1977). Further experiments in nearly homogeneous turbulent shear flow. Journal of Fluid Mechanics, 81(4), 657-687. doi:10.1017/s0022112077002286Hasslberger, J., Ketterl, S., Klein, M., & Chakraborty, N. (2018). Flow topologies in primary atomization of liquid jets: a direct numerical simulation analysis. Journal of Fluid Mechanics, 859, 819-838. doi:10.1017/jfm.2018.845Hinze, J. O. (1955). Fundamentals of the hydrodynamic mechanism of splitting in dispersion processes. AIChE Journal, 1(3), 289-295. doi:10.1002/aic.690010303Lasheras, J. C., & Hopfinger, E. J. (2000). Liquid Jet Instability and Atomization in a Coaxial Gas Stream. Annual Review of Fluid Mechanics, 32(1), 275-308. doi:10.1146/annurev.fluid.32.1.275Lebas, R., Menard, T., Beau, P. A., Berlemont, A., & Demoulin, F. X. (2009). Numerical simulation of primary break-up and atomization: DNS and modelling study. International Journal of Multiphase Flow, 35(3), 247-260. doi:10.1016/j.ijmultiphaseflow.2008.11.005Lee, K., Girimaji, S. S., & Kerimo, J. (2008). Validity of Taylor’s Dissipation-Viscosity Independence Postulate in Variable-Viscosity Turbulent Fluid Mixtures. 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Characterization of the pressure losses in a common rail diesel injector

A methodology to characterise the pressure losses in quasi-steady conditions (i.e. at full needle lift) of common rail diesel injectors was developed. The aim was to quantify the error when experimental results of nozzle internal flow are compared with CFD results, where pressure losses are usually neglected. The proposed methodology is based mainly on experimental tests that are complemented with some approximate calculations, based on the physics of the phenomenon, to take into account the effect of the needle deformation. The results obtained in the work lead to two important conclusions: on the one hand, that it is dangerous to extrapolate results relative to the injection (internal flow, spray atomization, spray penetration˙ ..) and combustion processes from low permeability nozzles (e.g. single-hole nozzles) to high permeability nozzles (e.g. multi-hole nozzles), and, on the other hand, that the comparison of these results between experiments and CFD simulations should be carried out carefully, because the pressure losses in the injector can be high under certain conditions. Finally, people working on the study of the injection and/or combustion processes, through experiments or simulations, will find here some interesting information to better know the actual injection pressure to be used in their analysis and/or simulations.The PhD studies of Oscar A. de la Garza were funded by the FPU program of the Ministerio de Educacion of Spain (grant no. AP2008-01913).López, JJ.; Salvador Rubio, FJ.; De La Garza De Leon, O.; Arregle, JJP. (2012). Characterization of the pressure losses in a common rail diesel injector. Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering. 226(12):1697-1706. https://doi.org/10.1177/0954407012447020S169717062261

Sensing with coupled-core optical fiber Bragg gratings

[EN] Sensitive bending and vibration sensors based on a coupled-core optical fiber with Bragg gratings are proposed and demonstrated. The interrogation of such sensors is cost effective without comprising the sensors performance.This work was supported by the Spanish Ministry of Science and Innovation under projects No. PGC2018-101997-B100 and RTI2018-0944669-BC31 and the Universitat Politècnica de València with the scholarship PAID-01-18.Flores-Bravo, JA.; Madrigal-Madrigal, J.; Zubia, J.; Margulis, W.; Sales Maicas, S.; Villatoro, J. (2021). Sensing with coupled-core optical fiber Bragg gratings. Optica Publishing Group. 1-2. https://doi.org/10.1364/FIO.2021.FM2C.21

Growth and growth hormone secretion in children with cancer treated with chemotherapy

To evaluate the effect of chemotherapy on growth and growth hormone (GH) secretion. METHODS: We analyzed growth and GH secretion in 60 children in complete remission after treatment by chemotherapy and surgery for malignant solid tumors. None of them received cranial radiotherapy. Growth hormone reserve was assessed by at least two stimulation tests (clonidine, L-dopa, growth hormone-releasing hormone). In 12 children the reserve of GH pretreatment was also evaluated. RESULTS: Growth hormone deficiency (GHD) was observed in 27 of 60 patients (45%). At diagnosis, mean standing height was +0.23 +/- 0.11 standard deviation score (SDS) in the GHD group and +0.16 +/- 0.10 SDS in the non-GHD group. After chemotherapy, mean standing height in the GHD group was -0.28 +/- 0.15 SDS and -0.14 +/- 0.11 in the non-GHD group (p < 0.05), and the growth rate was +0.13 +/- 0.07 SDS in the GHD group and +0.22 +/- 0.18 SDS in the non-GHD group. For a mean follow-up of 30 months, the mean standing height was -0.46 +/- 0.29 SDS in the GHD group and -0.24 +/- 0.16 SDS for the non-GHD group (p < 0.05), and the growth rate was -0.27 +/- 0.19 SDS in the GHD group and -0.16 +/- 0.12 SDS in the non-GHD group (p < 0.05). The GH response to clonidine was significantly less than that found with the other stimuli. There was correlation between the dose intensity of some drugs and the subsequent GH response to stimulation tests. The GHD group was found to have received significantly higher doses of actinomycin D than the non-GHD group (p < 0.05). Growth impairment and GHD were not found to be correlated with duration of treatment and follow-up, tumor type, sex, or age. CONCLUSIONS: Chemotherapy as the sole form of treatment in children with cancer interferes with growth. The observed impairment of growth depends, at least in part, on a GHD related to chemotherapy. The growth rate in conjunction with the GH response to clonidine provides a sensitive measure of GHD associated with chemotherapy